Wednesday, July 15, 2015
Grand Hall and Gallery, Ground Floor & 1st Floor (Maritim Hotel)
Ashleigh Goethel
,
University of Toronto, Toronto, Ontario, Canada
Sandrine Rouquier
,
Faculty of Medicine, University of Toronto, Toronto, ON, Canada
Galliano Zanello
,
Faculty of Medicine, University of Toronto, Toronto, ON, Canada
Dana Philpott
,
Department of Immunology, University of Toronto, Toronto, ON, Canada
Ken Croitoru, MD
,
Department of Immunology, University of Toronto, Toronto, ON, Canada
Inflammatory bowel diseases (IBD) are multifactorial diseases, involving genetic mutations, alterations of the gut microbiota and environmental triggers. The strongest genetic association is with nucleotide-binding oligomerization domain-containing protein 2 (NOD2), a pattern recognition receptor that recognizes a component of the bacterial cell wall. During adulthood, environmental perturbations, such as antibiotics, induce transient shifts in the microbiota composition. We sought to determine whether antibiotic‐induced dysbiosis in a NOD2 deficient mouse could lead to an altered immune response against the microbiota.
Adult WT and NOD2-/- mice received amoxicillin [200mg/L] ad libitum in drinking water for 7 days, followed by control water for 4 weeks. Fecal samples were collected to monitor changes in microbiota. On day 35, acute polyclonal T cell activation was induced by i.p. anti-CD3.
Bacterial load, measured using targeted qPCR for RNA polymerase B (rpoB), was significantly reduced at day 7; returning to pre-treatment levels by day 14 in both WT and NOD2-/- mice. At day 35, NOD2-/- mice had a significantly enhanced IL-17 response following anti-CD3 treatment, which was reduced with antibiotic treatment. This suggests that antibiotic alteration of murine adult microbiota in NOD2-/- mice leads to an altered immune response to the commensal gut microbiota.
